The ubiquitin-proteasome pathway and proteasome inhibitors

Authors

  • Jayhyuk Myung,

    1. Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut 06520-8103
    Search for more papers by this author
  • Kyung Bo Kim,

    1. Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut 06520-8103
    Search for more papers by this author
  • Craig M. Crews

    Corresponding author
    1. Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut 06520-8103
    2. Department of Pharmacology, Yale University, New Haven, Connecticut 06520-8103
    • Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut 06520-8103.
    Search for more papers by this author

Abstract

The ubiquitin-proteasome pathway has emerged as a central player in the regulation of several diverse cellular processes. Here, we describe the important components of this complex biochemical machinery as well as several important cellular substrates targeted by this pathway and examples of human diseases resulting from defects in various components of the ubiquitin-proteasome pathway. In addition, this review covers the chemistry of synthetic and natural proteasome inhibitors, emphasizing their mode of actions toward the 20S proteasome. Given the importance of proteasome-mediated protein degradation in various intracellular processes, inhibitors of this pathway will continue to serve as both molecular probes of major cellular networks as well as potential therapeutic agents for various human diseases. © 2001 John Wiley & Sons, Inc. Med Res Rev, 21, No. 4, 245–273, 2001

Ancillary